Yonsei Med J.  2019 Jan;60(1):106-114. 10.3349/ymj.2019.60.1.106.

Lennox-Gastaut Syndrome in Mitochondrial Disease

Affiliations
  • 1Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea. ymleemd@yuhs.ac
  • 2Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
Previous studies have shown that neurologic symptoms are dominant in patients with mitochondrial diseases, and most of these patients have seizure-related disorders. The epileptic classification of these patients as Lennox-Gastaut syndrome (LGS) is as high as 25%. This study aimed to investigate the clinical manifestations, diagnoses, treatments, and epilepsy in LGS, which is associated with mitochondrial disease.
MATERIALS AND METHODS
A retrospective study was conducted on 372 patients who were diagnosed with mitochondrial disease between 2006 and 2016. Of these 372 patients, 40 patients diagnosed with LGS were selected, and they were classified into two groups based on the history of West syndrome. Patient characteristics were reviewed, and associations between clinical factors and outcomes after the treatment were analyzed.
RESULTS
The proportion of individuals with mitochondrial disease with LGS with a history of West syndrome was 32.5%. Among the patients with mitochondrial disease with LGS, neonatal seizure (p=0.029), seizure as the first symptom (p=0.018), and generalized paroxysmal fast activity frequency on electroencephalogram (p=0.018) in the group with a history of West syndrome were statistically significantly high. The first symptom onset (0.6±0.4 yrs vs. 1.6±0.9 yrs, p=0.003) and first seizure onset (0.9±0.7 yrs vs. 3.9±3.1 yrs, p < 0.001) were significantly faster in patients with a history of West syndrome.
CONCLUSION
Close monitoring of the medical condition and early intervention might improve the prognosis of individuals with mitochondrial disease with LGS and a history of West syndrome.

Keyword

Lennox-Gastaut syndrome; mitochondrial disease; West syndrome; pediatric; children

MeSH Terms

Child
Classification
Diagnosis
Early Intervention (Education)
Electroencephalography
Epilepsy
Humans
Infant
Infant, Newborn
Mitochondrial Diseases*
Neurologic Manifestations
Prognosis
Retrospective Studies
Seizures
Spasms, Infantile

Reference

1. Scaglia F, Towbin JA, Craigen WJ, Belmont JW, Smith EO, Neish SR, et al. Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics. 2004; 114:925–931. PMID: 15466086.
Article
2. Darin N, Oldfors A, Moslemi AR, Holme E, Tulinius M. The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA abnormalities. Ann Neurol. 2001; 49:377–383. PMID: 11261513.
Article
3. Eom S, Lee HN, Lee S, Kang HC, Lee JS, Kim HD, et al. Cause of death in children with mitochondrial diseases. Pediatr Neurol. 2017; 66:82–88. PMID: 27843091.
Article
4. Lee YM, Kang HC, Lee JS, Kim SH, Kim EY, Lee SK, et al. Mitochondrial respiratory chain defects: underlying etiology in various epileptic conditions. Epilepsia. 2008; 49:685–690. PMID: 18266755.
Article
5. Gastaut H, Roger J, Ouahchi S, Timsit M, Broughton R. An electroclinical study of generalized epileptic seizures of tonic expression. Epilepsia. 1963; 4:15–44. PMID: 13963212.
Article
6. Arzimanoglou A, French J, Blume WT, Cross JH, Ernst JP, Feucht M, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009; 8:82–93. PMID: 19081517.
Article
7. Camfield PR. Definition and natural history of Lennox-Gastaut syndrome. Epilepsia. 2011; 52(Suppl 5):3–9.
Article
8. Bernier FP, Boneh A, Dennett X, Chow CW, Cleary MA, Thorburn DR. Diagnostic criteria for respiratory chain disorders in adults and children. Neurology. 2002; 59:1406–1411. PMID: 12427892.
Article
9. Lee HN, Eom S, Kim SH, Kang HC, Lee JS, Kim HD, et al. Epilepsy characteristics and clinical outcome in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Pediatr Neurol. 2016; 64:59–65. PMID: 27671241.
Article
10. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017; 58:512–521. PMID: 28276062.
11. Koene S, Jansen M, Verhaak CM, De Vrueh RL, De Groot IJ, Smeitink JA. Towards the harmonization of outcome measures in children with mitochondrial disorders. Dev Med Child Neurol. 2013; 55:698–706. PMID: 23489006.
Article
12. Heiskala H. Community-based study of Lennox-Gastaut syndrome. Epilepsia. 1997; 38:526–531. PMID: 9184597.
Article
13. Trevathan E, Murphy CC, Yeargin-Allsopp M. Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children. Epilepsia. 1997; 38:1283–1288. PMID: 9578523.
Article
14. Khurana DS, Salganicoff L, Melvin JJ, Hobdell EF, Valencia I, Hardison HH, et al. Epilepsy and respiratory chain defects in children with mitochondrial encephalopathies. Neuropediatrics. 2008; 39:8–13. PMID: 18504675.
Article
15. Debray FG, Lambert M, Chevalier I, Robitaille Y, Decarie JC, Shoubridge EA, et al. Long-term outcome and clinical spectrum of 73 pediatric patients with mitochondrial diseases. Pediatrics. 2007; 119:722–733. PMID: 17403843.
Article
16. El Sabbagh S, Lebre AS, Bahi-Buisson N, Delonlay P, Soufflet C, Boddaert N, et al. Epileptic phenotypes in children with respiratory chain disorders. Epilepsia. 2010; 51:1225–1235. PMID: 20196775.
Article
17. Gastraut H, Roger J, Soulayrol R, Tassinari CA, Régis H, Dravet C, et al. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as “petit mal variant”) or Lennox syndrome. Epilepsia. 1966; 7:139–179. PMID: 4959714.
18. Hancock EC, Cross HJ. Treatment of Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2009; 3:CD003277.
Article
19. Borggraefe I, Noachtar S. Pharmacotherapy of seizures associated with Lennox-Gastaut syndrome. Clin Med Insights Ther. 2010; 2:15–24.
Article
20. Blume WT. Pathogenesis of Lennox-Gastaut syndrome: considerations and hypotheses. Epileptic Disord. 2001; 3:183–196. PMID: 11844713.
21. Goldsmith IL, Zupanc ML, Buchhalter JR. Long-term seizure outcome in 74 patients with Lennox-Gastaut syndrome: effects of incorporating MRI head imaging in defining the cryptogenic subgroup. Epilepsia. 2000; 41:395–399. PMID: 10756403.
Article
22. Oguni H, Hayashi K, Osawa M. Long-term prognosis of Lennox-Gastaut syndrome. Epilepsia. 1996; 37(Suppl 3):44–47. PMID: 8681912.
Article
23. Oguni H. What is Lennox-Gastaut syndrome in the modern era? Neurol Asia. 2010; 15(Supple 1):9–10.
24. Weinmann HM. Lennox-Gastaut syndrome and its relationship to infantile spasms (West syndrome). In : Neidermeyer E, Degen R, editors. The Lennox-Gastaut syndrome. New York: Alan R Liss Inc.;1988. p. 301–316.
25. Eom S, Lee YM. Preliminary study of neurodevelopmental outcomes and parenting stress in pediatric mitochondrial disease. Pediatr Neurol. 2017; 71:43–49. PMID: 28476522.
Article
26. Pavone P, Striano P, Falsaperla R, Pavone L, Ruggieri M. Infantile spasms syndrome, West syndrome and related phenotypes: what we know in 2013. Brain Dev. 2014; 36:739–751. PMID: 24268986.
Article
27. Berg AT, Levy SR, Novotny EJ, Shinnar S. Predictors of intractable epilepsy in childhood: a case-control study. Epilepsia. 1996; 37:24–30. PMID: 8603620.
Article
28. von Kleist-Retzow JC, Cormier-Daire V, Viot G, Goldenberg A, Mardach B, Amiel J, et al. Antenatal manifestations of mitochondrial respiratory chain deficiency. J Pediatr. 2003; 143:208–212. PMID: 12970634.
Article
29. Gibson K, Halliday JL, Kirby DM, Yaplito-Lee J, Thorburn DR, Boneh A. Mitochondrial oxidative phosphorylation disorders presenting in neonates: clinical manifestations and enzymatic and molecular diagnoses. Pediatrics. 2008; 122:1003–1008. PMID: 18977979.
Article
30. Jasper H, Kershman J. Electroencephalographic classification of the epilepsies. Arch Neur Psych. 1941; 45:903–943.
Article
31. Dulac O, N'Guyen T. The Lennox-Gastaut syndrome. Epilepsia. 1993; 34(Suppl 7):S7–S17. PMID: 8243377.
Article
32. Halász P. Runs of rapid spikes in sleep: a characteristic EEG expression of generalized malignant epileptic encephalopathies. A conceptual review with new pharmacological data. Epilepsy Res Suppl. 1991; 2:49–71. PMID: 1662048.
33. Aydin-Özemir Z, Matur Z, Bebek N, Gürses C, Gökyiğit A, Baykan B. Long-term follow-up of adult patients with genetic generalized epilepsy with typical absence seizures and generalized paroxysmal fast activity in their EEG. Seizure. 2014; 23:607–615. PMID: 24908140.
Article
34. Yagi K. Evolution of Lennox-Gastaut syndrome: a long-term longitudinal study. Epilepsia. 1996; 37(Suppl 3):48–51. PMID: 8681913.
Article
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr